Voice disorders that affect more than two million Americans are associated with failures of vocal fold tissue in the face of osmotic, chemical, mechanical, and pathogenic threats. Current treatments are inadequate. Virtually all medical treatments focus on wound healing or repair, long after chronic vocal fold injury has occurred and voice, airway protection, or patency are compromised. Threat avoidance (vocal hygiene) has largely failed to prevent disorders so that voice loss contributes substantially to job absenteeism and social isolation. Our goal is to promote vocal fold tissue defenses against disease and injury, thereby preventing voice disorders. Healthy vocal fold epithelia possess mechanisms to defend against superficial threats by regulating the ionic and osmotic transepithelial water fluxes that protect the vocal fold surface. This work translates basic knowledge of the "defensive" hydration system into a novel aerosol to prevent voice disorders. Using biotransport, electrophysiologic, and behavioral assays, the experiments aim to identify candidate therapeutics with sufficient short-term activity, in vitro and in vivo, to justify immediate efficacy studies. As no personal aerosol delivery system is specific to the human larynx, industrial and clinical partners collaborate in the development of a drug delivery system, thus providing a practical approach to improve patient self-dosing performance. In humans at risk of voice disorder, a chemically optimized therapeutic (versus placebo control) will be delivered in a randomized, double-blind design to inhibit vocal sensitivity to dry-air, oral breathing challenge. This work offers the first aerosol for prevention of voice disorders and may also benefit persons suffering with ill-conditioned air supply or unavoidable environmental exposures. Prevention of voice disorders will eliminate substantial societal costs associated with medical and rehabilitative care for persons who are unable to communicate by voice, use voice communication technology, or join a voice-dependent workforce. [unreadable] [unreadable] [unreadable]